Cardiovascular disease is the greatest epidemic in healthcare today, claiming roughly 20% of all hospital admissions and 200,000 deaths annually. Various medical and surgical treatment options have been proposed, but only cardiac transplantation has shown long-term success. With only 2000 cardiac transplant cases performed annually, however, new therapeutic strategies are desperately needed. Heart failure is a progressive disease characterized by ventricular dilation leading to regional and global functional impairment. Compensatory mechanisms to preserve cardiac output in the failing heart result in increased levels of ventricular wall stress and overall cardiac workload. As the remodeling alters ventricular geometry, myocardial function continues to deteriorate and ultimately refractory heart failure develops. Currently, there are two broad categories of treatment strategies for heart failure being developed- cellular and mechanical, each holding therapeutic promise. In cellular therapy, exogenous cells (stem cells) are transplanted to the damaged myocardium to replete the dysfunctional cardiac myocytes. Although the exact mechanism is controversial, stem cell therapy has been shown to reduce infarct size and improve cardiac function. The Sponsor (Chen) and Co-Sponsor (Liao) have developed a biosynthetic scaffold composed of Type I collagen which delivers stem cells directly to the heart. Moreover, the composition of the scaffold is specifically optimized to promote adherence to the myocardium;thereby increasing stem cell migration and differentiation. In restraint therapy, a promising mechanical treatment, pressure is applied to the ventricle during end- diastole to reduce myocardial wall stress and reverse ventricular remodeling. Our group has developed a unique ventricular restraint device capable of applying adjustable and measurable restraint therapy to the heart. Using this device, an optimal level of ventricular restraint for the prevention of pathological remodeling has been identified and shown to reverse pathological remodeling. We now hypothesize that combining cellular therapy and ventricular restraint therapy will have a synergistic improvement on heart failure. To date, mechanical therapy and cellular therapy together have yet to be studied. By treating the damaged heart with two dichotomous but synergistic approaches, our group hopes to provide a realistic treatment option for heart failure. With the 1-year mortality rate of 20% in patients with congestive heart failure, this research would have a substantial impact on public health, much as combination drug therapy for drug resistant microbial pathogens has done.